Modulation of Inhaled Antigen-Induced IgE Tolerance by Ongoing Th2 Responses in the Lung

Abstract

The normal response to inhaled Ag is the absence of Ag-specific IgE and cytokine production to later Ag challenges. Although the mechanism of this aerosol-induced IgE tolerance is not completely understood, it may prevent sensitization to inhaled Ags, which could otherwise lead to allergy and asthma. We examined the consequences of ongoing Th1 and Th2 responses in the lungs of mice during OVA inhalation to mimic conditions that may subvert tolerance and lead to sensitization. We found that concurrent, secondary Th2 lung responses to keyhole limpet hemocyanin or primary responses to Nippostrongylus larvae or Asperigillus fumagatus extract prevented establishment of IgE tolerance to aerosolized OVA. Intranasal rIL-4 given before OVA aerosolization also prevented establishment of tolerance, whereas concurrent Th1 responses to influenza virus or Mycobacterium bovis bacillus Calmette-Guérin had no effect. However, once established, aerosol tolerance to OVA could not be completely broken by OVA rechallenge concurrent with a secondary Th2 response to keyhole limpet hemocyanin or A. fumagatus extract, or by intranasal rIL-4. These data suggest that the immune status of the lung of an individual may profoundly influence the initial response to inhaled Ag, and that aerosol-induced IgE tolerance may not be appropriately established in individuals undergoing concurrent, Th2-mediated responses to Ags or pathogens.

Influenza A Virus Infection Inhibits the Efficient Recruitment of Th2 Cells into the Airways and the Development of Airway Eosinophilia

“…However, the opposite seems to be true, because most epidemiological studies show a clear association between infections with respiratory viruses and the exacerbation of asthma in humans (11)(12)(13)(14). Animal experiments addressing this issue have yielded somewhat conflicting results with some reports indicating that respiratory viral infections increase allergen-induced Th2 responses in the lung and others reporting no effect or a suppressive effect (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). For this reason, we investigated how an intranasal (i.n.)…”

“…However, although infections with respiratory viruses induce Th1 immune responses, most epidemiological studies indicate that viral infections are associated with the exacerbation and not the inhibition of asthma in humans (11, 13, 14). Furthermore, animal experiments addressing this issue have yielded somewhat conflicting results with some reports indicating that viral infections can both increase or suppress allergen-induced Th2 responses in the lung, depending upon the virus used and the time point of infection (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). The aim of our study was to analyze whether an infection with flu virus interfered with the development of Th2 responses in the lung induced by the recruitment of Th2 cells into the airways after the i.n.…”

“…infection with flu virus influenced the development of allergen-induced Th2 responses in the lung of mice. In contrast to most previously published reports addressing similar questions (15,22,25,26), we used an OVA immunization protocol where the initial allergenspecific Th2 response does not develop in the lung. The allergenspecific Th2 response is induced by an OVA/alum protocol, leading to the recruitment of Th2 cells into the airways and resulting in airway eosinophilia, mucus production, and AHR.…”

A Protease-Activated Pathway Underlying Th Cell Type 2 Activation and Allergic Lung Disease

“…Allergic inflammation of the lung is not induced when OVA is given only through the airway (18), and lack of T effector responses persists even with subsequent priming with the same Ag and adjuvant (19). However, allergic reactions to other Ags are not affected in rodents tolerized to OVA (20). Thus, rather than an abnormal response with general effects on immunity, tolerance to inhaled Ag may be regarded as a highly selective, Ag-specific immune response that may have evolved as a means of protection against inappropriate immune activation in the lung.…”

Significados culturais da asma infantil

“…The dynamic, experimentally based characteristic of this phase seems to be forgotten. 2,3,6 More years of schooling would propitiate knowledge of preventive health measures that reduce morbidity due to respiratory disease as well as a set of more appropriate actions with respect to child care. 7 Given that one of the principal foundations of prevention and control of asthma is the educational process, it is necessary to become familiar with the social and cultural characteristics of the asthmatic child's mother /carer that seeks the emergency ward of the hospital during a crisis.…”